Wrinkles Gone? New Uses Studied for Botox

By DONALD G. McNEIL Jr.

Published: March 2, 2003

It is probably premature to declare Botox the penicillin of the 21st century, but the deadly poison turned wrinkle remover is being put to some startling new uses.

In studies around the world, botulinum toxin is being tested -- often with encouraging results -- as a treatment for stroke paralysis, migraine headaches, facial tics, stuttering, lower back pain, incontinence, writer's cramp, carpal tunnel syndrome and tennis elbow.

Scientists are testing its ability to treat morbid obesity by weakening the muscle that lets food out of the stomach, to prevent ulcers by weakening the muscles that force gastric acids into the esophagus and to calm spasms in vaginal muscles that make sex painful. Botox is rescuing newborns with clubfoot from surgery and giving patients with spastic vocal cords back their voices.

Some trials are nearly ready for submission to the federal Food and Drug Administration; others are small and preliminary. But the toxin ''has enormous potential'' for relaxing muscles and treating some pain, including headaches, said Dr. Robert B. Daroff, the former editor in chief of Neurology magazine, who said he does not use botulinum toxin in his Cleveland neurology practice but became a believer after seeing migraine patients improve.

Dr. Jean Carruthers, an ophthalmologist at the University of British Columbia, compared it to penicillin for its versatility against a wide range of ills, and because it, too, is an organic product derived from a common bacterium. With her husband, Arthur, a dermatologist, she was one of the first to observe, in 1987, that the small doses she injected to paralyze and relax her patients' spastic eye muscles also smoothed their brows.

The toxin has many advantages over other paralyzing and painkilling agents. It acts only where it is injected. It can be used merely to weaken a muscle instead of paralyzing it. It lasts for months, but it does wear off, so mistakes are reversible. In 25 years of use, it has harmed very few patients, and then only under rare circumstances.

A spokeswoman for the F.D.A. declined to discuss uses that the agency has not yet formally approved, but said the toxin was considered ''very safe'' for approved uses like making frown lines disappear. There were ''some examples where it was injected in the wrong places, but those problems were temporary,'' said Lenore Gelb, referring a reporter to the drug's warning labels.

The labeling indicates ''rare spontaneous reports of deaths,'' mostly from pneumonia. Doctors familiar with the toxin said they seemed to occur in people with undiagnosed neuromuscular diseases like myasthenia gravis. Also, they said, some patients who had too much injected into deep neck muscles temporarily lost their ability to swallow and had to be fed by gastric tubes. But to give a normal patient a fatal dose would require injecting at least 35 vials, Dr. Carruthers said.

''Every medical specialty is finding a niche for this drug,'' said Dr. Richard G. Glogau, a dermatologist at the University of California at San Francisco who in 2000 published a study showing that his wrinkle treatments were also curing his patients' migraine headaches.

Because it can even paralyze glands, the toxin could find uses as an injectable deodorant and a treatment for flop sweat.

At Ludwig-Maximilian University in Munich, panelists who sniffed circles cut from the sleeves of T-shirts of 16 men who had been injected with botulinum toxin in one armpit and saline solution in the other found the toxin armpit odor less unpleasant.

Several studies have shown reductions in hyperhydrosis, which is not mere clammy palms but the dripping-faucet kind of sweating that rots shoe soles and ruins business deals and love lives.

The toxin is ''one of the most amazing compounds we've seen in the last two decades,'' said Dr. Marc Heckmann, a Munich dermatologist who led two sweat-control studies. He compared it in importance to the discoveries of corticosteroids and chemotherapy.

Now virtually any muscle that can spasm, producing painful or embarrassing reactions, is being experimented upon.

Doctors are devising new deep-body injection techniques: syringes attached to flexible scopes or to probes that detect electrical impulses in muscles.

Three months ago, Beatrice F. Brunger, 79, of Chicago was suffering from incontinence, and had suffered for three years. As often as four times a night, she had to get up as the muscle walls of her bladder went into spasms -- a common cause of incontinence among the elderly.

''Then I couldn't get back to sleep,'' Mrs. Brunger said. ''My strength was going steadily downhill. I wouldn't go out for lunch or dinner or a movie -- I was just too tired.''

Detrol and Ditropan, the usual drugs for the condition, did not work. Normally, Mrs. Brunger would have faced a daunting operation: up to three hours of surgery to make a hole in the side of her bladder and build a ''reserve tank'' of intestine material.

Instead, Dr. Gregory T. Bales, a urological surgeon with the University of Chicago Hospital, used a cystoscope with a camera and a minute syringe to travel up her urethra and inject the inside walls of her bladder with three vials of Botox -- more than triple the amount used to smooth forehead wrinkles.

''It takes five minutes,'' he said. ''We make 20 to 25 injections. A full bladder is about the size of a cantaloupe, and each injection takes care of about the size of a quarter.''

Mrs. Brunger said she came home an hour later, had no pain, and since then has slept through the night. The only side effect is that, during the day, it takes somewhat longer to urinate.

''Botox is neat,'' Dr. Bales said. ''We're doing 15 patients a day.''

The one drawback, he said, is that his study is so new that he does not know how long it lasts. In cosmetic use, it wears off in six to eight months.

In Vancouver, British Columbia, Dr. Christine M. Alvarez, a pediatric orthopedic surgeon, treats clubfoot, a twisting inward of the heel and toe that affects up to 1 in 500 infants.